In a randomized double-blind multicenter clinical study, 116 children with asthma were randomly assigned to treatment with an inhaled beta-2-agonist (salbutamol 0.2 mg) plus an inhaled corticosteroid (budesonide 0.2 mg) three times a day (BA+CS) or to an inhaled beta-2-agonist (salbutamol 0.2 mg) plus a placebo three times a day (BA+PL). After a median follow-up time of 22 months, 26 patients receiving BA+PL (45%) had withdrawn from randomized treatment, mainly because of asthma symptoms, compared with three withdrawals in the patients receiving BA+CS (p less than 0.0001). The FEV1, expressed as a percentage of the predicted value for age, sex, and height, showed an absolute increase of 7.0% after 2 months of BA+CS compared with a decrease of 4.0% after 2 months of BA+PL. This 11% difference in percent predicted FEV1 (95% confidence interval, 7 to 15%; p less than 0.0001) was then maintained after a median follow-up period of 22 months. Postbronchodilator FEV1 showed an absolute increase of 3.7% predicted within 2 months in patients receiving BA+CS and an absolute decrease of 1.1% predicted in children receiving BA+PL (p = 0.0005). Thereafter, this difference between the two treatment groups was maintained. Average peak expiratory flow rate (PEFR) increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min in the BA+PL group (p = 0.003). This difference then remained for the median follow-up time of 22 months.(ABSTRACT TRUNCATED AT 250 WORDS)

It was concluded that participation in the physical exercise programme not only enhanced physical fitness, but also improved coping behaviour with asthma.

Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age, who had completed 28 to 36 months of treatment with inhaled corticosteroid (budesonide 200 micrograms 3 times/day) and inhaled beta-2-agonist (salbutamol 200 micrograms 3 times/day). The children were randomized in a 1:2 ratio in a double-blind study either to continue budesonide (n = 8) during a period of 6 months or to decrease the dose of budesonide (n = 20) within 2 months, followed by placebo for 4 months. Treatment with salbutamol 600 micrograms daily was continued in both groups. Eight children from the tapering-off group withdrew, mainly due to symptoms of asthma, compared with none in the continuous treatment group. Five patients in the tapering-off group experienced exacerbations for which prednisolone was given, compared with none in the continuous treatment group. After tapering-off, symptoms of asthma and additional bronchodilator use increased, and both FEV1% predicted and PD20 histamine (provocation dose of histamine causing a 20% fall in FEV1) decreased, whereas these all remained unchanged in the group that continued treatment with inhaled corticosteroid. We conclude that in this study long-term treatment with 600 micrograms budesonide daily suppressed underlying mechanisms of asthma, but did not cure the disease.

As minute volume increases with age, a study was carried out to determine whether the measurement of bronchial responsiveness to pharmacological agents with the tidal breathing technique in children might be influenced by age. Bronchial responsiveness to histamine administered by tidal breathing was therefore compared with that produced with a dosimeter in 25 children with asthma aged 5-18 years. Bronchial responsiveness was defined as the concentration ofhistamine that caused a 40% rise in pulmonary resistance (PC40) measured by random noise forced oscillation at 6 Hz. Values of PC40 measured by the tidal breathing method were lower than those obtained with the dosimeter method, presumably owing to differences in the dose administered and variations in the pattern of breathing. The difference between the two methods was not related to age, however. It iq concluded that the tidal breathing and the dosimeter methods are both suitable for the measurement of bronchial responsiveness in children of various ages and that both can be used in longitudinal studies.

In an incremental cost-effectiveness analysis, combined inhaled beta 2-receptor agonist plus inhaled corticosteroid therapy (BA + CS) was compared with inhaled beta 2-agonist plus placebo (BA + PL) in 116 asthmatic children aged 7 to 16 years. Clinical data have been reported previously. To account for the selective withdrawal rate due to pulmonary problems that occurred in the group receiving BA + PL, costs were calculated using 2 approaches: (1) the cumulative cost approach and (2) the patient-year approach. Besides improvements in forced expiratory volume in 1 second (FEV 1) and airway responsiveness expressed as the provocative dose of histamine required to give a 20% fall in FEV 1 (PD 20), the frequency of asthma symptoms and school absenteeism were significantly reduced in the BA + CS group. Annual drug acquisition costs for the group receiving BA + CS were NLG480 higher than for the BA + PL group ($US1 = NLG2.12, 1989 prices). Based on conservative calculations using the cumulative cost approach, annual savings due to reduced healthcare utilisation, excluding the cost of study drugs, by the group receiving BA + CS compared with BA + PL were estimated to be about NLG273 per patient. The incremental cost effectiveness of BA + CS was estimated to be about NLG175 per 10% increase in FEV 1, or somewhat less than NLG10 per symptom-free day gained. The patient-year approach estimated savings due to corticosteroids of about 43% of the costs of BA + PL (95% confidence intervals, 21 to 58%). Savings were larger when the indirect costs that a family incurred during school absenteeism were considered. Addition of an inhaled corticosteroid to an inhaled beta 2-receptor agonist is a cost-effective treatment option that could even result in net healthcare savings.